Findings

This mutation was originally found in three generations of a family of Romanian origin by a research group at Indiana University School of Medicine. The average age of onset was 45.7 years (Murrell et al., 1991). It was later found in an Austrian individual (known as P. 31) of Romanian ancestry with a disease onset of approximately 38 years, as well as in two German siblings (known as P.32 and P.65) with onset at 40 and 37 years, respectively (Finckh et al., 2005).

Neuropathology

Unknown.

Biological Effect

Studies in cell culture have shown that the V717F mutation generally increases the Aβ42/Aβ40 ratio in conditioned media. COS cells expressing mutant APP695 secreted approximately equal levels of Aβ40 and Aβ42/43. This represented an increase in the Aβ42(43)/Aβ40 ratio, as cells expressing wild-type APP secreted predominantly Aβ40 (Tamaoka et al., 1994). A similar result was reported in M17 human neuroblastoma cells. Compared with cells expressing wild-type APP, cells transfected with APP V717F secreted relatively more Aβ42/43 than Aβ40 (Suzuki et al., 1994). A study focused primarily on the E693G “Arctic” APP mutation showed that HEK293 cells transfected with APP V717F produced an elevated Aβ42/Aβ40 ratio due to both an increase in secreted Aβ42 and a decrease in Aβ40 (Nilsberth et al., 2001).

Other mutations at this position

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